The accurate measurement of blood flow and blood perfusion is of great clinical importance for evaluating physiologic function and clinical conditions. Noninvasive Doppler sonography has been used to provide information on blood velocity and techniques have been developed to estimate volumetric blood flow rates from Doppler velocity measurements. Measurement of volumetric blood flow using traditional Doppler generally requires the determination of vessel size, beam/vessel angle and some estimate of the spatial variations in velocity. These requirements limit the accuracy of volumetric flow rate assessments because of the many sources of error in the velocity estimation using Doppler methods, such as errors in the estimation of vessel diameter and beam/vessel angle.
Ultrasonic contrast agents, which most commonly take the form of encapsulated gaseous micro-bubbles, which scatter ultrasound effectively, have been demonstrated to enhance ultrasonic images of blood and Doppler signals. With recent improvements in their ability to persist over longer periods of time, ultrasonic contrast agents hold great potential for improved blood flow and perfusion measurements in local tissue regions and organs. As their interactions with ultrasound are radically different from blood or soft tissue, the application of ultrasonic contrast agents opens new ground for developing new and better methods for quantification and characterization of fluid flow.
Ultrasound contrast agents can be used as blood volume contrast agents because they become distributed within the vascular space, travel at the same velocity as the blood flow rate or velocity, and remain relatively stable in the body during clinical observation periods. These characteristics provide the potential for mean flow rate estimation based on the indicator dilution principle using the contrast time-video intensity curve in ultrasonic images following a bolus injection. Such a process is described in the article "Mathematical Modeling of the Dilution Curves for Ultrasonic Contrast Agents," by C. M. Sehgal et al., J. Ultrasound Med., 16:471-479, 1997. However, current ultrasound methods that use the time-intensity curve in ultrasonic images following a bolus injection of a contrast medium are somewhat limited at present because 1) the interaction of ultrasound with contrast agents is not well understood; 2) the lack of knowledge of the number concentration of contrast agent and the rate of delivery, sometimes referred to as the "input function"; and 3) video intensity in ultrasonic images is a nonlinear conversion of returned echo amplitude from scatterers. Thus, improved methods of flow rate measurement using such contrast agents are required.